Combinatorial Synthesis of Deoxyhexasaccharides Related to the Landomycin A Sugar Moiety, Based on an Orthogonal Deprotection Strategy

Abstract

In this report, we describe the stereoselective synthesis of a combinatorial library comprised of 16 deoxyhexasaccharides that are related to a landomycin A sugar moiety, based on an orthogonal deprotection strategy. The use of an olivosyl donor containing a benzyl ether at the C3 position and benzoyl ester at the C4 position, and the olivosyl donor, a naphthylmethyl ether, and a p-nitrobenzylethyl or benzyl sulfonyl ester enabled the synthesis of a set of four diolivosyl units containing a hydroxyl group at the C3 or C4 position by a simple glycosylation and deprotection procedure. Using a phenylthio 2,3,6-trideoxyglycoside, alpha-selective glycosidation proceeded without anomerization of the 2,6-dideoxy-beta-glycosides. In addition, alkylhydroquinone and levulinoyl groups were found to be an effective set of orthogonal protecting groups for the anomeric position and a hydroxyl group. The coupling of all combinations of trisaccharide units in a beta-selective manner was accomplished by activation of the glycosyl imidate with I(2) and Et(3)SiH. No cleavage of the acid-labile 2,3,6-trideoxyglycoside was observed under the conditions used for the reactions. Finally, all of the protected hexasaccharides were deprotected by hydrolysis of the esters, microwave (MW) assisted cleavage of the 2-trimethylsilylethoxymethoxy (SEM) ether, and a Birch reduction.

Stereoselective Formation of 2‐Deoxyglycosidic Bonds in Biologically Active Natural Products

“…[18][19][20] As shown in Scheme 38.9, treatment of the 4-O-benzylsulfonylolivosyl imidate 21 and 23 with I 2 and a catalytic amount of triethylsilane in toluene at À94 C provided the 2-deoxy-b-glycoside 24 in 94% yield with a nearly complete b selectivity (a/b ¼ 5/>95). [18][19][20] As shown in Scheme 38.9, treatment of the 4-O-benzylsulfonylolivosyl imidate 21 and 23 with I 2 and a catalytic amount of triethylsilane in toluene at À94 C provided the 2-deoxy-b-glycoside 24 in 94% yield with a nearly complete b selectivity (a/b ¼ 5/>95).…”

Mild Method for 2-Naphthylmethyl Ether Protecting Group Removal Using a Combination of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and β-Pinene

“…All other chemicals were purchased at the highest possible quality and used as received. Compounds 4 , 21 6 , 21 8 , 22 10 , 23 15 , 24 20 , 25 23 , 26 27 , 27 and 30 (25) were prepared according to literature methods…”

“…The spectroscopic data is in good agreement with previously reported data. 25 1 H NMR (500 MHz, CDCl 3 ) δ 7.36 (d, J = 4.4 Hz, 4H), 7.35–7.26 (m, 1H), 6.35 (dd, J = 6.2, 1.5 Hz, 1H), 4.85 (dd, J = 6.1, 2.2 Hz, 1H), 4.71 (d, J = 11.7 Hz, 1H), 4.55 (d, J = 11.8 Hz, 1H), 4.05 (dt, J = 7.1, 1.9 Hz, 1H), 3.90 (dq, J = 9.2, 6.3 Hz, 1H), 3.62 (ddd, J = 9.3, 7.0, 3.6 Hz, 1H), 2.19 (d, J = 3.6 Hz, 1H), 1.39 (d, J = 6.4 Hz, 3H).…”

Tackling the Challenges in the Total Synthesis of Landomycin A

“…Tanaka and co‐workers found that 2,6‐dideoxyglycosyl trichloroacetimidates could undergo highly β‐selective glycosylation under the promotion of I 2 /Et 3 SiH at low temperatures (−94 °C) [18] . By adopting this procedure, they achieved the synthesis of a number of deoxyoligosaccharides, including landomycin A hexasaccharide derivative 51 () [19] . Thus, coupling olivose acceptor 42 with olivosyl imidate 43 in the presence of I 2 and a catalytic amount of Et 3 SiH at −78 °C provided disaccharide 44 in 75% yield with excellent β selectivity (β/α = 93:7).…”